Comparative proteomics in the corpus callosal sub-regions of postmortem human brain

Kashem, Mohammed A.; Sarker, Ranjana; Etages, Huyghues Des; Machaalani, Rita; King, Nicholas J. C.; McGregor, Iain S.; Matsumoto, Izuru

doi:10.1016/j.neuint.2009.04.017

Cited by 13 publications

(3 citation statements)

References 52 publications

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“…Different proteomic profiles across subregions of the corpus callosum have been reported, with greater similarity between the genu and body compared with the splenium [30]. In addition, the anatomy and neuronal fiber origination of the genu and body are more similar compared with the splenium [31-33].…”

Section: Discussionmentioning

confidence: 99%

White matter integrity and executive abilities in individuals with phenylketonuria

Antenor-Dorsey

Hershey

Rutlin

et al. 2013

Molecular Genetics and Metabolism

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Previous studies have revealed white matter abnormalities in the brains of individuals with phenylketonuria (PKU), but the microstructural nature of these abnormalities and their relationship to phenylalanine (Phe) levels and cognitive outcomes is poorly understood. In the current study, the microstructural integrity of white matter in 29 individuals with early-treated PKU and 12 healthy controls was examined using two complementary diffusion tensor imaging (DTI) approaches: region-of-interest (ROI) based analysis and voxel-wise tract based spatial statistics (TBSS) analysis. Relationships among DTI, executive abilities, and Phe level findings were explored. DTI revealed widespread lowering of mean diffusivity (MD) in the white matter of the PKU group in comparison with the control group. Executive abilities were also poorer for individuals with PKU than controls. Within the PKU group, lower MD was associated with higher Phe level and poorer executive abilities. These findings are the first to demonstrate the interplay among microstructural white matter integrity, executive abilities, and Phe control in individuals with PKU.

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Section: Discussionmentioning

confidence: 99%

White matter integrity and executive abilities in individuals with phenylketonuria

Antenor-Dorsey

Hershey

Rutlin

et al. 2013

Molecular Genetics and Metabolism

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“…We isolated a novel protein, (ARL1), which was downregulated in response to THC exposure. Alcohol and methamphetamine administration similarly alter expression of this protein (Iwazaki et al, 2008; Kobeissy et al, 2008; Kashem et al, 2009). ARL1 is a Ras GTPase involved in retrograde trafficking of endosomes between the Golgi apparatus and the membrane in mammalian cells (Nishimoto-Morita et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: a hippocampal proteomic study in mice

Spencer

Darbyshire

Boucher³

et al. 2013

Front. Cell. Neurosci.

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Neuregulin 1 (NRG1) is linked to an increased risk of developing schizophrenia and cannabis dependence. Mice that are hypomorphic for Nrg1 (Nrg1 HET mice) display schizophrenia-relevant behavioral phenotypes and aberrant expression of serotonin and glutamate receptors. Nrg1 HET mice also display idiosyncratic responses to the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol (THC). To gain traction on the molecular pathways disrupted by Nrg1 hypomorphism and Nrg1-cannabinoid interactions we conducted a proteomic study. Adolescent wildtype (WT) and Nrg1 HET mice were exposed to repeated injections of vehicle or THC and their hippocampi were submitted to 2D gel proteomics. Comparison of WT and Nrg1 HET mice identified proteins linked to molecular changes in schizophrenia that have not been previously associated with Nrg1. These proteins are involved in vesicular release of neurotransmitters such as SNARE proteins; enzymes impacting serotonergic neurotransmission, and proteins affecting growth factor expression. Nrg1 HET mice treated with THC expressed a distinct protein expression signature compared to WT mice. Replicating prior findings, THC caused proteomic changes in WT mice suggestive of greater oxidative stress and neurodegeneration. We have previously observed that THC selectively increased hippocampal NMDA receptor binding of adolescent Nrg1 HET mice. Here we observed outcomes consistent with heightened NMDA-mediated glutamatergic neurotransmission. This included differential expression of proteins involved in NMDA receptor trafficking to the synaptic membrane; lipid raft stabilization of synaptic NMDA receptors; and homeostatic responses to dampen excitotoxicity. These findings uncover novel proteins altered in response to Nrg1 hypomorphism and Nrg1-cannabinoid interactions that improves our molecular understanding of Nrg1 signaling and Nrg1-mediated genetic vulnerability to the neurobehavioral effects of cannabinoids.

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“…Protein extraction and gel analysis were conducted according to the method previously described [21,22]. In brief, *50 mg of fresh frozen piglet hippocampal tissue from one hemisphere was homogenized in 1 ml of Buffer 1 [7 M urea, 2 M thiourea, 1% 3-(4-Heptyl)phenyl-3-hydroxypropyl] dimethylammoniopropanesulfonate (C7bZO) and 40 mM Tris-HCl).…”

Section: Sample Preparationmentioning

confidence: 99%

Intermittent Hypercapnic Hypoxia Induced Protein Changes in the Piglet Hippocampus Identified by MALDI-TOF-MS

et al. 2009

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Intermittent hypercapnic hypoxia (IHH) induces protein changes in the brainstem, but its effects on the hippocampus have not yet been studied. Using a proteomics-based approach, we tested the hypothesis that IHH up-regulates apoptotic promoters and down-regulates apoptotic inhibitors in the developing hippocampus. Male piglets aged 13-14 days were assigned to control (n = 6) or IHH (n = 5) groups. Using two-dimensional polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS), a total of 26 protein spots were differentially expressed in IHH compared to control group. Thirteen of these (6 up-regulated, 7 down-regulated) were identified including 14-3-3θ/τ (increased), glial fibrillary acidic protein (increased) and a-internexin (decreased). Further analysis with western blot validated these proteins and immunohistochemistry showed specific regional changes in the subiculum, stratum radiatum and CA1 of the hippocampus. Most proteins identified were involved in promoting cell survival under apoptotic conditions. These findings improve our understanding of the cellular processes that occur in the hippocampus during IHH exposure, and have important implications in clinical settings where IHH is experienced, for example, during prone sleeping or with obstructive sleep apnea in an infant.

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Comparative proteomics in the corpus callosal sub-regions of postmortem human brain

Cited by 13 publications

References 52 publications

White matter integrity and executive abilities in individuals with phenylketonuria

White matter integrity and executive abilities in individuals with phenylketonuria

Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: a hippocampal proteomic study in mice

Intermittent Hypercapnic Hypoxia Induced Protein Changes in the Piglet Hippocampus Identified by MALDI-TOF-MS

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